Lucia Gozzo | Università di Catania (original) (raw)

Papers by Lucia Gozzo

Research paper thumbnail of The anatomical therapeutic chemical classification is flexible enough to describe the innovation in biotechnological drugs?

Research Square (Research Square), Feb 7, 2023

The Anatomical-Therapeutic-Chemical Classi cation (ATC)-de ned by the WHO as a "tool for drug uti... more The Anatomical-Therapeutic-Chemical Classi cation (ATC)-de ned by the WHO as a "tool for drug utilization monitoring and research in order to improve quality of drug use"-codes active substances and groups them according to the target organ or system and their therapeutic, pharmacological and chemical properties. However, the classi cation could include inconsistencies, mostly evident for biotechnological products, resulting in possible inappropriate use. The work aimed at determining whether drugs (in particular biologics) are appropriately described by their ATC code,investigating evidence on their use and suggesting solutions to improve the classi cation pattern. METHODS: Twelve experts critically analyzed the ATC classi cation and proposed possible solutions. The results were summarized in statements, which were voted to reach a consensus through the Nominal Group Technique. Each expert voted on the statements, and the agreement was de ned at 75% of the highest scores. Additionally, to investigate the use of ATC in scienti c research, a literature review of its use was also performed. RESULTS: Based on a literature review, a total of 75 studies were analyzed; 99% concerned the appropriate use of ATC classi cation. Then, based on their experience, the experts identi ed the following inconsistencies in the ATC code: use of a single ATC code for more than one indication; lack of identi cation of differences among drug formulations deriving from their pharmacokinetic pro le and differences attributable to further characteristics, beyond indication of use and mechanism of action (e.g., blood coagulation factors). Ten statements were identi ed: 5 regarding critical issues in the ATC code (structural limits at the ATC fth code level; time-consuming, complex, imprecise coding request/modi cation procedure) and 5 possible solutions (telematic procedures to modernize the request/modi cation ATC code process; unique form to request/modify codes, specifying manufacturing process and reference to therapeutic equivalence among active principles; further levels beyond the V to differentiate drug peculiarities). Agreement among experts was reached for all statements. CONCLUSIONS: The ATC code classi cation pattern should be partially changed to incorporate the peculiarities of biotechnologies to promote their appropriate use.

Research paper thumbnail of Starting dose and dose adjustment of Non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation

Research Square (Research Square), Dec 29, 2020

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in pa... more This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with AF. In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. Methods We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. Results During the reference period, treatment was commenced for 866539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA₂DS₂-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Conclusions Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Research paper thumbnail of Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries

IJC Heart & Vasculature, Feb 1, 2020

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an inc... more Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in ''non-valvular atrial fibrillation" (NVAF). Methods: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with ''NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. Results: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. Conclusions: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Research paper thumbnail of Beyond the budget silo approach: estimating health system sustainability for future dementia drugs

Pharmadvances, 2020

Aim of the study: to analyze the impact of a hypothetic disease-modifying drug (DMD) on the estim... more Aim of the study: to analyze the impact of a hypothetic disease-modifying drug (DMD) on the estimated costs of dementia sustained by the National Health System (NHS) based on current real-world data. We performed our analysis on the Caserta Local Health Unit (LHU) database and the ARNO Observatory, which include data from 19 Italian LHUs. Participants with at least 1 year of database history and a diagnosis of dementia were identified using the ICD-9CM codes for dementia in the hospital discharge diagnosis, specific exemption codes and prescriptions of anti-dementia drugs. An assessment of the actual healthcare costs was performed using available data on all healthcare services reimbursed by the NHS in the reference period. Finally, we made prevalence projection for Caserta's and for ARNO's population and estimated the number of new cases avoided by decreasing the incidence of 20% and 40% five years after the introduction of DMD in 2025. Average annual cost per patient with dementia equaled € 2,193 for the Caserta LHU and € 4,356 for the ARNO LHUs. The NHS 5-years savings was equal to € 4,057,050 and € 8,116,293 for Caserta, and € 96,563,808 and € 193,127,616 for ARNO, considering a 20% and 40% reduction of dementia incidence after the introduction of the hypothetical new anti-dementia drug in 2025. Our study forecasts the impact of future prevalence on health management based on real-world prevalence and expenditure data and provides a useful model to project theoretical savings after the introduction of a new DMD for dementia and for other unmet medical needs. Although comparable by sample type and selection criteria, the estimated difference in disease expenditures from the two databases indicates that the method of generating costs could be linked to a distinct health management in LHUs.

Research paper thumbnail of Innovation in Ocular Pharmacology

Frontiers Research Topics

Research paper thumbnail of Editorial: Innovative treatments for neuro-psychiatric diseases

Frontiers in Neuroscience

Research paper thumbnail of Fluoxetine Protects Retinal Ischemic Damage in Mice

Pharmaceutics

Background: To evaluate the neuroprotective effect of the topical ocular administration of fluoxe... more Background: To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. Methods: Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. Results: PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the e...

Research paper thumbnail of The therapeutic value of treatment for multiple sclerosis: analysis of health technology assessments of three European countries

Frontiers in Pharmacology

In accordance with European regulation, medicines containing a new active substance to treat neur... more In accordance with European regulation, medicines containing a new active substance to treat neurodegenerative diseases as well as autoimmune and other immune dysfunctions must be approved by the European Medicines Agency (EMA) through the centralized procedure before they can be marketed. However, after EMA approval, each country is responsible for national market access, following the assessment performed by health technology assessment (HTA) bodies with regard to the therapeutic value. This study aims to provide a comparative analysis of HTA recommendations issued by three EU countries (France, Germany, and Italy) for new drugs for multiple sclerosis (MS) following EMA approval. In the reference period, we identified 11 medicines authorized in Europe for MS, including relapsing forms of MS (RMS; n = 4), relapsing–remitting MS (RRMS; n = 6), secondary progressive MS (SPMS; n = 1), and the primary progressive form (PPMS; n = 1). We found no agreement on the therapeutic value (in pa...

Research paper thumbnail of Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data

Healthcare

Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mu... more Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis. Furthermore, serious GI disorders have been observed with gilteritinib in clinical trials, including GI hemorrhage, GI perforation and GI obstruction. However, the association with the FLT3 inhibitor has not been confirmed. Nevertheless, serious GI AEs have been recognized as an important potential risk to be monitored in postmarketing surveillance. We present three cases of serious self-limiting GI...

Research paper thumbnail of Periodontal Disease and Pregnancy: Correlation with Underweight Birth

European Journal of Dentistry

Periodontal disease is a risk factor for many systemic diseases including preterm birth and under... more Periodontal disease is a risk factor for many systemic diseases including preterm birth and underweight birth. The purpose of this systematic review is to analyze the literature and to highlight any clinical correlation. Information sources such as PubMed, MEDLINE, and Web of Science were consulted to obtain our results with these keywords “periodontal disease,” “pregnancy,” “weight loss” using the connector “AND.” After the first screening by authors, only 27 articles were included in this review. From the analysis of the literature, it was noted that the presence of periodontal disease could have a correlation with underweight birth. Surely, control oral hygiene and oral health is essential during pregnancy to reduce risks, and these results should be essential in establishing a protocol to be maintained during pregnancy.

Research paper thumbnail of Bioequivalence, Drugs with Narrow Therapeutic Index and The Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution

Healthcare

The prescription of generic drugs represents one of the main cost-containment strategies of healt... more The prescription of generic drugs represents one of the main cost-containment strategies of health systems, aimed at reducing pharmaceutical expenditure. In this context, most regulatory authorities encourage or obligate dispensing generic drugs because they are far less expensive than their brand-name alternatives. However, drug substitution can be critical in particular situations, such as the use of drugs with a narrow therapeutic index (NTI). Moreover, generics cannot automatically be considered bioequivalent with each other due to the biocreep phenomenon. In Italy, the regulatory authority has established the Transparency Lists which include the medications that will be automatically substituted for brand-name drugs, except in exceptional cases. This is a useful tool to guide prescribers and guarantee pharmaceutical sustainability, but it does not consider the biocreep phenomenon.

Research paper thumbnail of Efficacy and safety of subthreshold micropulse laser compared with threshold conventional laser in central serous chorioretinopathy

Eye, 2019

PurposeTo compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold c... more PurposeTo compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in central serous chorioretinopathy (CSC).MethodsProspective, randomized, double-masked, non-inferiority, 12-week clinical trial. Patients were randomly assigned 1:1 to SML group or TCL group. Patients in the SML group were treated with 577 nm micropulse laser. The spot size was 160 µm, the duty cycle was 5% and exposure time was 0.2 s. The power was 50% threshold tested. Patients in the TCL group were treated with 577 nm continuous laser. The power was 100% threshold tested. The primary outcome was the mean change in best-corrected visual acuity (BCVA) at week 12, with a non-inferiority limit of five letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts.ResultsEighty-eight patients were enroled. Seventy-seven patients were male. Forty-four patients were in SML group and 44 in TCL group. At week 12, SML was equivalent to TCL with a...

Research paper thumbnail of Towards a European harmonization of health technology assessment recommendations executive paper of European regulatory conference focused on the EU commission proposal to harmonize HTA

Frontiers in Drug Safety and Regulation

Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision... more Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision-making”, including those related to drug reimbursement and price negotiation based on comprehensive clinical and non-clinical evaluations. The discrepancies in HTA recommendations among European countries are related to the differences in health care systems and willingness to invest in health care, differences in assessment methodologies and appraisal practices, and variations in economic constraints, and may produce disparities in terms of patient access to medicines. The political discussion about the adoption of the European Regulation on HTA lasted for years due to concerns about its feasibility and its implications for national health care systems In this paper we highlighted the importance to harmonize HTA process in Europe and some critical issues emerged during the discussion among experts in the field carried out at the European Regulatory Conference.

Research paper thumbnail of Access to Innovative Neurological Drugs in Europe: Alignment of Health Technology Assessments Among Three European Countries

Frontiers in Pharmacology

Even for products centrally approved, each European country is responsible for national market ac... more Even for products centrally approved, each European country is responsible for national market access after European Medicines Agency (EMA) approval. This step can result in inequalities in terms of access, due to different opinions about the therapeutic value assessed by Health Technology Assessment (HTA) bodies. This study aims to provide a comparative analysis of HTA recommendations issued by EU countries (France, Germany, and Italy) for new neurological drugs following EMA approval. In the reference period, we identified 11 innovative medicines authorized in Europe for five neurological diseases (cerebral adrenoleukodystrophy, spinal muscular atrophy, metachromatic leukodystrophy, migraine, and polyneuropathy in patients with hereditary transthyretin amyloidosis), including eight drugs for genetic rare diseases. We found no agreement on the therapeutic value (in particular the “added value” compared to the standard of care) of the selected drugs. Despite the differences in terms...

Research paper thumbnail of Attitude survey of spontaneous adverse drug-reaction reporting by general practitioners in Sicily

Bullettin of the Gioenia Academy of Natural Sciences of Catania

Spontaneous adverse drug reaction (ADR) reporting is fundamental for drug safety surveillance. Ho... more Spontaneous adverse drug reaction (ADR) reporting is fundamental for drug safety surveillance. However, under-reporting is one of the main limitations of the pharmacovigilance system and may cause bias for data interpretation. The purpose of the present study was to assess the general practitioners’ (GPs) knowledge about Pharmacovigilance in Sicily (Italy) and their spontaneous reporting attitude, in order to identify the reasons for under-reporting, and to determine which steps to pursue to increase the reporting rates. A self-administered questionnaire has been sent to a sample of 440 GPs in Sicily. After two weeks, the same questionnaire was administered by telephone to non-responders. When the response rate was significantly high (> 40%), data were evaluated. Four-hundred-and-forty GPs were contacted, but only 41.3% of them completed the interviews. Reasons for under-reporting included ‘lack of time’, ‘lack of adequate feed-back by the Pharmacovigilance’s Service’, ‘fear of l...

Research paper thumbnail of Pegylated Asparaginase‐Induced Liver Injury: A Case‐Based Review and Data From Pharmacovigilance

The Journal of Clinical Pharmacology

Treatment of acute lymphoblastic leukemia has changed since introducing the asparaginase drug and... more Treatment of acute lymphoblastic leukemia has changed since introducing the asparaginase drug and its pegylated form, i.e., pegasparaginase. Several trials have demonstrated a clear advantage in using this drug in adolescents and young adults, up to 60 years. However, this drug possesses a unique plethora of side effects, spanning from pancreatitis to coagulopathy, including hepatotoxicity. This could be of mild intensity but can lead to life-threatening sequelae, up to death. Here, we report a case of a 59 years old patient affected by acute lymphoblastic leukemia, who eventually died cause of pegasparaginase-related hepatotoxicity. A review of the available literature will be provided, including epidemiology, pathophysiology and possible therapeutic interventions. In the end, an analysis of the Italian pharmacovigilance database will be presented, where hepatotoxicity has been reported in 32 cases (10% of reported adverse events, including 3 deaths related to drug-induced liver damage). This article is protected by copyright. All rights reserved.

Research paper thumbnail of Regulatory, scientific, and ethical issues arising from institutional activity in one of the 90 Italian Research Ethics Committees

BMC Medical Ethics, 2021

Background This paper highlights the issues that one of the 90 Italian Research Ethics Committees... more Background This paper highlights the issues that one of the 90 Italian Research Ethics Committees (RECs) might encounter during the approval phase of a clinical trial to identify corrective and preventive actions for promoting a more efficient review process and ensuring review quality. Publications on the subject from Italy and the rest of Europe are limited; encouraging constructive debate can improve RECs’ service to the subject of the clinical trial. Methods We retrospectively reviewed a cohort of 822 clinical trial protocols, initially reviewed by REC, from June 2014 to December 2018. Data collected for each protocol were type of trial, sample size, use of placebo, number and kind of revisions requested by the REC before approval, and time taken for approval. Data for each protocol were collected by a trained clinical research assistant using the REC’s files and electronic archives. Results Almost 45% of the reviewed studies (374/822) required clarifications, significant change...

Research paper thumbnail of Fertility Preservation in Female Pediatric Patients With Cancer: A Clinical and Regulatory Issue

Frontiers in Oncology, 2021

Fertility preservation represents one important goal of cancer patients’ management due to the hi... more Fertility preservation represents one important goal of cancer patients’ management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues. Supporting data demonstrate a significant advantage for the survivors who received GnRHa in the long-term maintenance of ovarian function and preservation of fertility. The prevention of the risk of ovarian failure with GnRHa is a typical off-label use, defined as the administration of a medicinal product not in accordance with the authorized product information. Italy has officially recognized the off-label use of GnRHa in adult women at risk of premature and permanent menopause following chem...

Research paper thumbnail of The Regulatory Challenges for Drug Repurposing During the Covid-19 Pandemic: The Italian Experience

Frontiers in Pharmacology, 2020

Research paper thumbnail of How many chronic myeloid leukemia patients who started a frontline second‐generation tyrosine kinase inhibitor have to switch to a second‐line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA)

Cancer Medicine, 2020

on behalf of the AIFA's Monitoring Registries Group 5 This is an open access article under the te... more on behalf of the AIFA's Monitoring Registries Group 5 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of The anatomical therapeutic chemical classification is flexible enough to describe the innovation in biotechnological drugs?

Research Square (Research Square), Feb 7, 2023

The Anatomical-Therapeutic-Chemical Classi cation (ATC)-de ned by the WHO as a "tool for drug uti... more The Anatomical-Therapeutic-Chemical Classi cation (ATC)-de ned by the WHO as a "tool for drug utilization monitoring and research in order to improve quality of drug use"-codes active substances and groups them according to the target organ or system and their therapeutic, pharmacological and chemical properties. However, the classi cation could include inconsistencies, mostly evident for biotechnological products, resulting in possible inappropriate use. The work aimed at determining whether drugs (in particular biologics) are appropriately described by their ATC code,investigating evidence on their use and suggesting solutions to improve the classi cation pattern. METHODS: Twelve experts critically analyzed the ATC classi cation and proposed possible solutions. The results were summarized in statements, which were voted to reach a consensus through the Nominal Group Technique. Each expert voted on the statements, and the agreement was de ned at 75% of the highest scores. Additionally, to investigate the use of ATC in scienti c research, a literature review of its use was also performed. RESULTS: Based on a literature review, a total of 75 studies were analyzed; 99% concerned the appropriate use of ATC classi cation. Then, based on their experience, the experts identi ed the following inconsistencies in the ATC code: use of a single ATC code for more than one indication; lack of identi cation of differences among drug formulations deriving from their pharmacokinetic pro le and differences attributable to further characteristics, beyond indication of use and mechanism of action (e.g., blood coagulation factors). Ten statements were identi ed: 5 regarding critical issues in the ATC code (structural limits at the ATC fth code level; time-consuming, complex, imprecise coding request/modi cation procedure) and 5 possible solutions (telematic procedures to modernize the request/modi cation ATC code process; unique form to request/modify codes, specifying manufacturing process and reference to therapeutic equivalence among active principles; further levels beyond the V to differentiate drug peculiarities). Agreement among experts was reached for all statements. CONCLUSIONS: The ATC code classi cation pattern should be partially changed to incorporate the peculiarities of biotechnologies to promote their appropriate use.

Research paper thumbnail of Starting dose and dose adjustment of Non-vitamin K antagonist oral anticoagulation agents in a nationwide cohort of patients with atrial fibrillation

Research Square (Research Square), Dec 29, 2020

This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in pa... more This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with AF. In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. Methods We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. Results During the reference period, treatment was commenced for 866539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA₂DS₂-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Conclusions Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Research paper thumbnail of Non-vitamin K antagonist oral anticoagulation agents in patients with atrial fibrillation: Insights from Italian monitoring registries

IJC Heart & Vasculature, Feb 1, 2020

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an inc... more Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased risk of stroke and thromboembolism. Anticoagulation with Vitamin K antagonists (VKAs) or with novel oral anti-coagulants (NOACs) represents the cornerstone of the pharmacological treatment to reduce the risk of thromboembolism. This study aims to provide real-world data from a whole large European country about NOAC use in ''non-valvular atrial fibrillation" (NVAF). Methods: We analysed the Italian Medicines Agency (AIFA) monitoring registries collecting data of a nationwide cohort of patients with ''NVAF" treated with NOACs. Using logistic regression analysis, baseline characteristics and treatment discontinuation information were compared among initiators of the 4 NOACs. Results: In the reference period, the NOAC database collected data for 683,172 patients. The median age was 78 years with 19.5% aged 85 or older. Overall, the treatments were in accordance with guidelines. About 1/3 of patients switched from a prior VKA treatment; in the 72.3% of cases, these patients had a labile International Normalized Ratio (INR) at first prescription. The most prescribed NOAC was rivaroxaban, followed by apixaban, dabigatran and edoxaban. Conclusions: This study is the largest European real-world study ever published on NOACs. It includes all Italian patients treated with NOACs since 2013 accounting for about 1/3 of subjects with AF. The enrolled population consisted of very elderly patients, at high risk of ischemic adverse events. The AIFA registries are consolidated tools that guarantee the appropriateness of prescription and provide important information for the governance of National Health System by collecting real-world data.

Research paper thumbnail of Beyond the budget silo approach: estimating health system sustainability for future dementia drugs

Pharmadvances, 2020

Aim of the study: to analyze the impact of a hypothetic disease-modifying drug (DMD) on the estim... more Aim of the study: to analyze the impact of a hypothetic disease-modifying drug (DMD) on the estimated costs of dementia sustained by the National Health System (NHS) based on current real-world data. We performed our analysis on the Caserta Local Health Unit (LHU) database and the ARNO Observatory, which include data from 19 Italian LHUs. Participants with at least 1 year of database history and a diagnosis of dementia were identified using the ICD-9CM codes for dementia in the hospital discharge diagnosis, specific exemption codes and prescriptions of anti-dementia drugs. An assessment of the actual healthcare costs was performed using available data on all healthcare services reimbursed by the NHS in the reference period. Finally, we made prevalence projection for Caserta's and for ARNO's population and estimated the number of new cases avoided by decreasing the incidence of 20% and 40% five years after the introduction of DMD in 2025. Average annual cost per patient with dementia equaled € 2,193 for the Caserta LHU and € 4,356 for the ARNO LHUs. The NHS 5-years savings was equal to € 4,057,050 and € 8,116,293 for Caserta, and € 96,563,808 and € 193,127,616 for ARNO, considering a 20% and 40% reduction of dementia incidence after the introduction of the hypothetical new anti-dementia drug in 2025. Our study forecasts the impact of future prevalence on health management based on real-world prevalence and expenditure data and provides a useful model to project theoretical savings after the introduction of a new DMD for dementia and for other unmet medical needs. Although comparable by sample type and selection criteria, the estimated difference in disease expenditures from the two databases indicates that the method of generating costs could be linked to a distinct health management in LHUs.

Research paper thumbnail of Innovation in Ocular Pharmacology

Frontiers Research Topics

Research paper thumbnail of Editorial: Innovative treatments for neuro-psychiatric diseases

Frontiers in Neuroscience

Research paper thumbnail of Fluoxetine Protects Retinal Ischemic Damage in Mice

Pharmaceutics

Background: To evaluate the neuroprotective effect of the topical ocular administration of fluoxe... more Background: To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. Methods: Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. Results: PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the e...

Research paper thumbnail of The therapeutic value of treatment for multiple sclerosis: analysis of health technology assessments of three European countries

Frontiers in Pharmacology

In accordance with European regulation, medicines containing a new active substance to treat neur... more In accordance with European regulation, medicines containing a new active substance to treat neurodegenerative diseases as well as autoimmune and other immune dysfunctions must be approved by the European Medicines Agency (EMA) through the centralized procedure before they can be marketed. However, after EMA approval, each country is responsible for national market access, following the assessment performed by health technology assessment (HTA) bodies with regard to the therapeutic value. This study aims to provide a comparative analysis of HTA recommendations issued by three EU countries (France, Germany, and Italy) for new drugs for multiple sclerosis (MS) following EMA approval. In the reference period, we identified 11 medicines authorized in Europe for MS, including relapsing forms of MS (RMS; n = 4), relapsing–remitting MS (RRMS; n = 6), secondary progressive MS (SPMS; n = 1), and the primary progressive form (PPMS; n = 1). We found no agreement on the therapeutic value (in pa...

Research paper thumbnail of Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data

Healthcare

Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mu... more Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis. Furthermore, serious GI disorders have been observed with gilteritinib in clinical trials, including GI hemorrhage, GI perforation and GI obstruction. However, the association with the FLT3 inhibitor has not been confirmed. Nevertheless, serious GI AEs have been recognized as an important potential risk to be monitored in postmarketing surveillance. We present three cases of serious self-limiting GI...

Research paper thumbnail of Periodontal Disease and Pregnancy: Correlation with Underweight Birth

European Journal of Dentistry

Periodontal disease is a risk factor for many systemic diseases including preterm birth and under... more Periodontal disease is a risk factor for many systemic diseases including preterm birth and underweight birth. The purpose of this systematic review is to analyze the literature and to highlight any clinical correlation. Information sources such as PubMed, MEDLINE, and Web of Science were consulted to obtain our results with these keywords “periodontal disease,” “pregnancy,” “weight loss” using the connector “AND.” After the first screening by authors, only 27 articles were included in this review. From the analysis of the literature, it was noted that the presence of periodontal disease could have a correlation with underweight birth. Surely, control oral hygiene and oral health is essential during pregnancy to reduce risks, and these results should be essential in establishing a protocol to be maintained during pregnancy.

Research paper thumbnail of Bioequivalence, Drugs with Narrow Therapeutic Index and The Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution

Healthcare

The prescription of generic drugs represents one of the main cost-containment strategies of healt... more The prescription of generic drugs represents one of the main cost-containment strategies of health systems, aimed at reducing pharmaceutical expenditure. In this context, most regulatory authorities encourage or obligate dispensing generic drugs because they are far less expensive than their brand-name alternatives. However, drug substitution can be critical in particular situations, such as the use of drugs with a narrow therapeutic index (NTI). Moreover, generics cannot automatically be considered bioequivalent with each other due to the biocreep phenomenon. In Italy, the regulatory authority has established the Transparency Lists which include the medications that will be automatically substituted for brand-name drugs, except in exceptional cases. This is a useful tool to guide prescribers and guarantee pharmaceutical sustainability, but it does not consider the biocreep phenomenon.

Research paper thumbnail of Efficacy and safety of subthreshold micropulse laser compared with threshold conventional laser in central serous chorioretinopathy

Eye, 2019

PurposeTo compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold c... more PurposeTo compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in central serous chorioretinopathy (CSC).MethodsProspective, randomized, double-masked, non-inferiority, 12-week clinical trial. Patients were randomly assigned 1:1 to SML group or TCL group. Patients in the SML group were treated with 577 nm micropulse laser. The spot size was 160 µm, the duty cycle was 5% and exposure time was 0.2 s. The power was 50% threshold tested. Patients in the TCL group were treated with 577 nm continuous laser. The power was 100% threshold tested. The primary outcome was the mean change in best-corrected visual acuity (BCVA) at week 12, with a non-inferiority limit of five letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts.ResultsEighty-eight patients were enroled. Seventy-seven patients were male. Forty-four patients were in SML group and 44 in TCL group. At week 12, SML was equivalent to TCL with a...

Research paper thumbnail of Towards a European harmonization of health technology assessment recommendations executive paper of European regulatory conference focused on the EU commission proposal to harmonize HTA

Frontiers in Drug Safety and Regulation

Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision... more Health Technology Assessment (HTA) is a multidisciplinary process which supports policy “decision-making”, including those related to drug reimbursement and price negotiation based on comprehensive clinical and non-clinical evaluations. The discrepancies in HTA recommendations among European countries are related to the differences in health care systems and willingness to invest in health care, differences in assessment methodologies and appraisal practices, and variations in economic constraints, and may produce disparities in terms of patient access to medicines. The political discussion about the adoption of the European Regulation on HTA lasted for years due to concerns about its feasibility and its implications for national health care systems In this paper we highlighted the importance to harmonize HTA process in Europe and some critical issues emerged during the discussion among experts in the field carried out at the European Regulatory Conference.

Research paper thumbnail of Access to Innovative Neurological Drugs in Europe: Alignment of Health Technology Assessments Among Three European Countries

Frontiers in Pharmacology

Even for products centrally approved, each European country is responsible for national market ac... more Even for products centrally approved, each European country is responsible for national market access after European Medicines Agency (EMA) approval. This step can result in inequalities in terms of access, due to different opinions about the therapeutic value assessed by Health Technology Assessment (HTA) bodies. This study aims to provide a comparative analysis of HTA recommendations issued by EU countries (France, Germany, and Italy) for new neurological drugs following EMA approval. In the reference period, we identified 11 innovative medicines authorized in Europe for five neurological diseases (cerebral adrenoleukodystrophy, spinal muscular atrophy, metachromatic leukodystrophy, migraine, and polyneuropathy in patients with hereditary transthyretin amyloidosis), including eight drugs for genetic rare diseases. We found no agreement on the therapeutic value (in particular the “added value” compared to the standard of care) of the selected drugs. Despite the differences in terms...

Research paper thumbnail of Attitude survey of spontaneous adverse drug-reaction reporting by general practitioners in Sicily

Bullettin of the Gioenia Academy of Natural Sciences of Catania

Spontaneous adverse drug reaction (ADR) reporting is fundamental for drug safety surveillance. Ho... more Spontaneous adverse drug reaction (ADR) reporting is fundamental for drug safety surveillance. However, under-reporting is one of the main limitations of the pharmacovigilance system and may cause bias for data interpretation. The purpose of the present study was to assess the general practitioners’ (GPs) knowledge about Pharmacovigilance in Sicily (Italy) and their spontaneous reporting attitude, in order to identify the reasons for under-reporting, and to determine which steps to pursue to increase the reporting rates. A self-administered questionnaire has been sent to a sample of 440 GPs in Sicily. After two weeks, the same questionnaire was administered by telephone to non-responders. When the response rate was significantly high (> 40%), data were evaluated. Four-hundred-and-forty GPs were contacted, but only 41.3% of them completed the interviews. Reasons for under-reporting included ‘lack of time’, ‘lack of adequate feed-back by the Pharmacovigilance’s Service’, ‘fear of l...

Research paper thumbnail of Pegylated Asparaginase‐Induced Liver Injury: A Case‐Based Review and Data From Pharmacovigilance

The Journal of Clinical Pharmacology

Treatment of acute lymphoblastic leukemia has changed since introducing the asparaginase drug and... more Treatment of acute lymphoblastic leukemia has changed since introducing the asparaginase drug and its pegylated form, i.e., pegasparaginase. Several trials have demonstrated a clear advantage in using this drug in adolescents and young adults, up to 60 years. However, this drug possesses a unique plethora of side effects, spanning from pancreatitis to coagulopathy, including hepatotoxicity. This could be of mild intensity but can lead to life-threatening sequelae, up to death. Here, we report a case of a 59 years old patient affected by acute lymphoblastic leukemia, who eventually died cause of pegasparaginase-related hepatotoxicity. A review of the available literature will be provided, including epidemiology, pathophysiology and possible therapeutic interventions. In the end, an analysis of the Italian pharmacovigilance database will be presented, where hepatotoxicity has been reported in 32 cases (10% of reported adverse events, including 3 deaths related to drug-induced liver damage). This article is protected by copyright. All rights reserved.

Research paper thumbnail of Regulatory, scientific, and ethical issues arising from institutional activity in one of the 90 Italian Research Ethics Committees

BMC Medical Ethics, 2021

Background This paper highlights the issues that one of the 90 Italian Research Ethics Committees... more Background This paper highlights the issues that one of the 90 Italian Research Ethics Committees (RECs) might encounter during the approval phase of a clinical trial to identify corrective and preventive actions for promoting a more efficient review process and ensuring review quality. Publications on the subject from Italy and the rest of Europe are limited; encouraging constructive debate can improve RECs’ service to the subject of the clinical trial. Methods We retrospectively reviewed a cohort of 822 clinical trial protocols, initially reviewed by REC, from June 2014 to December 2018. Data collected for each protocol were type of trial, sample size, use of placebo, number and kind of revisions requested by the REC before approval, and time taken for approval. Data for each protocol were collected by a trained clinical research assistant using the REC’s files and electronic archives. Results Almost 45% of the reviewed studies (374/822) required clarifications, significant change...

Research paper thumbnail of Fertility Preservation in Female Pediatric Patients With Cancer: A Clinical and Regulatory Issue

Frontiers in Oncology, 2021

Fertility preservation represents one important goal of cancer patients’ management due to the hi... more Fertility preservation represents one important goal of cancer patients’ management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues. Supporting data demonstrate a significant advantage for the survivors who received GnRHa in the long-term maintenance of ovarian function and preservation of fertility. The prevention of the risk of ovarian failure with GnRHa is a typical off-label use, defined as the administration of a medicinal product not in accordance with the authorized product information. Italy has officially recognized the off-label use of GnRHa in adult women at risk of premature and permanent menopause following chem...

Research paper thumbnail of The Regulatory Challenges for Drug Repurposing During the Covid-19 Pandemic: The Italian Experience

Frontiers in Pharmacology, 2020

Research paper thumbnail of How many chronic myeloid leukemia patients who started a frontline second‐generation tyrosine kinase inhibitor have to switch to a second‐line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA)

Cancer Medicine, 2020

on behalf of the AIFA's Monitoring Registries Group 5 This is an open access article under the te... more on behalf of the AIFA's Monitoring Registries Group 5 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.